How does a single neuron establish and maintain many functionally distinct synapses? How are specific synaptic proteins added and removed from specific synapses to regulate signal transmission efficiency? Recent evidence suggests that changes in post-synaptic protein distribution constitute a cell biological mechanism leading to long term potentiation and long term depression, which are believed to form the basis of memory and learning. It was previously shown that a phylogenetically conserved PDZ-domain containing protein (LIN-10) is required for targeting of an AMPA-type glutamate receptor (GluR) to central synapses in C. elegans. This synaptic function of LIN- 10 is likely to be phylogenetically conserved since a human orthologue (X11/Mint) can functionally replace the endogenous worm protein. The goal of this proposal is to elucidate the mechanism by which LIN-10 regulates the abundance of GluR localization at post-synaptic elements as a step towards understanding the dynamic regulation of synaptic protein localization. A comparison with the function of LIN-10 in epithelial cells will test the hypothesis that a basic mechanism for protein localization is common in both cell types.